The texture of alkali-treated vegetable protein makes it suitable for producing meat substitutes to reduce intake of animal lipids. Feeding severely alkali-treated soy protein to growing rats has induced cytomegalia in the proximal tubules of the kidney. The amino acid derivative lysinoalanine (LAL) has been implicated in causing this nephrocytomegalia (NCM), proving much more active in free than in protein-bound form. Therefore factors affecting availability of LAL can be important risk factors for the rat. Three possible factors which occur in the rat but are virtually absent in man are: a very extensive gastrointestinal microflora, prolonged cecal retention of food residues, and coprophagy. Preliminary tests of severely alkali-treated soy protein in GF rats have shown a temporary severe diarrhea, followed by recovery and a slower development of NCM than occurs in the conventional (CV) rat. The rat microflora thus prevents diarrhea and hastens NCM. Analyses of gut contents are being carried out to correlate LAL availability at various gut levels with NCM severity. Feeding of free LAL to GF and CV rats and also in vitro studies will be used to look for other microflora effects which could reduce the availability of LAL. Depending on above results, rats with specific microfloras will also be tested. The influence of cecal retention and coprophagy on NCM induction and LAL availability in both GF and CV rats will be determined. The GF rat may provide a readily reproducible test system for further investigating the mechanism of NCM induction. These studies will aid in determining the applicability of the rat model to human consumers of alkali-treated vegetable proteins and the many other foods found to contain LAL.